Synthesis, in-vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2-hydroxymethylbenzimidazole as carrier ligands

• Published in: Journal of pharmacy and pharmacology Vol. 66; no. 11; pp. 1593 - 1605
• Main Authors: Utku, Semra, Özçelik, Azime Berna, Gümüş, Fatma, Yılmaz, Şükran, Arsoy, Taibe, Açık, Leyla, Çelebi Keskin, Ayten
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-11-2014; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; benzimidazole; Benzimidazoles - chemistry; Carboplatin - pharmacology; Carboplatin - therapeutic use; Cisplatin - pharmacology; Cisplatin - therapeutic use; cytotoxic activity; DNA - drug effects; DNA - metabolism; DNA binding; Drug Screening Assays, Antitumor; Estrogens - pharmacology; Estrogens - therapeutic use; gel electrophoresis; HeLa Cells; Humans; In Vitro Techniques; Ligands; MCF-7 Cells; Neoplasms - drug therapy; Plasmids - drug effects; Plasmids - genetics; Platinum - pharmacology; Platinum - therapeutic use; platinum(II) complexes; Progesterone - pharmacology; Progesterone - therapeutic use; Progestins - pharmacology; Progestins - therapeutic use; Restriction Mapping; benzimidazole; gel electrophoresis; cytotoxic activity; DNA binding; platinum(II) complexes
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12290

Objectives
The aim of this study was to investigate the in‐vitro cytotoxic activity of new platinum(II) complexes on the human HeLa (ER−), MCF‐7 (ER+) and MDA‐MB 231 (ER−) cell lines. Furthermore, we investigated plasmid DNA interactions and inhibition of BamHI and HindIII restriction enzyme activity of the complex 1–4,7.
Methods
Platinum(II) complexes were synthesised from precursor complexes of [PtL2Cl2] and [PtL2I2]. Their cytotoxic activity was tested by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Their plasmid DNA interactions and restriction enzyme activities were also investigated using the agarose gel electrophoresis method.
Key findings
The growth inhibitory effect results showed that the cytotoxicity of complex 2 was found to be the most active complex among the synthesised complexes.
Conclusions
The MTT results showed that complex 2 was found to be cytotoxic equal to cisplatin and higher than carboplatin against the MCF‐7 and MDA‐MB‐231 cell lines. Furthermore, the estrogen or progesterone co‐treatment slightly increased the cytotoxicity of complex 2, the cisplatin and carboplatin compared with the complex 2 tested alone in 50 μm concentration. According to plasmid DNA interaction and the restriction studies, complexes 1–4,7 modified the tertiary structure of pBR322 plasmid DNA, and complexes 2–4 prevented enzyme digestion at high concentrations.